Biology is in the midst of a revolution. An era dominated by the identification and characterization of parts- genes, proteins, organelles, cells-is giving way to one focused on complex interaction networks, principles of design, and the role of network function in the context of the entire organism. The immediate product of this revolution is an emerging field, Systems Biology, that breaks with the past not only in the types of questions it asks, but also in the diverse disciplines it draws heavily upon, including mathematics, computer science, engineering, and physics. This application requests renewal of a pre-doctoral training program designed to produce Ph.D.s prepared for careers in Systems Biology. The program was initially developed as part of a collaboration between the Howard Hughes Medical Institute and the NIH (NIBIB) to develop new, interdisciplinary Ph.D. training programs at the interface between the biological sciences and other disciplines. Eight predoctoral trainee slots are requested, for appointments intended to last two years each. Highlights of the program include an extensive didactic curriculum; a focus on critical thinking skills; an emphasis on collaboration and collaborative learning; close mentoring, opportunities to develop career skills; and active student involvement. The 43 program faculty members come from twelve different departments in five schools at the University of California, Irvine, and conduct research on diverse topics within Systems Biology. The program enjoys strong campus support, and an administrative and intellectual home within the UCI Center for Complex Biological Systems, an NIH-supported National Center for Systems Biology.